Cloned monkey embryos are a "gallery of horrors"

A high percentage of cloned monkey embryos that look healthy are really a "gallery of horrors" deep within, says a researcher at Advanced Cell Technology, the company that last month published the first paper on cloned human embryos.

This could mean that there is something unique about primate eggs that will make cloning monkeys or people far more difficult than cloning other animals. At the very least, the experiments show that there's a lot to learn before primates can be cloned.

Tanja Dominko, who presented the results last week at a conference in Washington DC, did the work before joining ACT, while she was working for the reproductive biologist Gerald Schatten at the Oregon Regional Primate Research Center in Beaverton.

Several groups have been trying for years to clone monkeys, but while the embryos look normal, no one has ever got them to develop further.

Uneven scatter

To try and figure out what was going wrong, Dominko looked at 265 cloned rhesus macaque embryos created by nuclear transfer - plucking out an egg's nucleus and then adding a nucleus from a donor cell. She followed development of the embryos through several divisions, from the two-cell stage until the 32-cell stage.

Though they appeared superficially healthy, the cells in the vast majority of Dominko's embryos did not form distinct nuclei containing all the chromosomes. Instead, the chromosomes were scattered unevenly throughout the cells.

"The surprising thing is that these cells keep dividing," says Dominko. Some embryos developed to the stage known as a blastocyst, but by day six or seven they had started to look abnormal.

The cloned human embryos created by ACT didn't even get this far. Only one reached the six-cell stage.

Trauma of removal

Dominko says that the trauma of removing the nucleus from the egg might be what triggers the defects. Eggs whose nuclei are removed and then put back inside show the same abnormalities, as well as evidence of programmed cell suicide. "This is not to say that normal embryos can't be made, but not on a regular basis," says Dominko.

Ian Wilmut, who cloned Dolly the sheep, told the conference that Dominko's results were not surprising in the light of experience of nuclear transfer in mice and cows. Even in these animals the success rates are not high, so the phenomena observed by Dominko probably occur in them as well - it's just that everyone focuses on the few successes, he says.

Even so, researchers hoping to publish work on nuclear transfer in humans may now have to come up with better evidence that embryos are healthy. William Haseltine, editor of the journal in which ACT published details of its cloned human embryos, now agrees that pictures alone aren't enough.

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